Our work is in two major areas. The first goal is to understand and then enhance differential toxicity between transformed and normal cells. We are working with lines of normal and transformed human cells in culture and have shown that a metabolic inhibitor will protect normal but not transformed cells from killing by a cycle specific agent leading to a greatly enhanced therapeutic ratio. We have shown that some of the nitrosoureas selectively kill transformed human cells more than normal and we are attempting to elucidate the mechanisms involved. We have done preliminary work suggesting that the differential toxicity of BCNU for transformed cells can be enhanced by X-ray. Our second goal has been to describe the relationship between toxicity and mutagenicity for a number of classes of anti-tumor agents in cultured mammalian cells. We have correlated these biological data with DNA single-strand breaks and crosslinks. Our goal is to find DNA lesions produced by certain agents that retain toxicity and anti-tumor activity but lack mutagenic and carcinogenic activity. As a ramification of this work we have shown that fluorescent light is highly mutagenic to mammalian cells and that it causes DNA single-strand breaks, some types of which may result in toxicity and mutagenicity and others of which do not. BIBLIOGRAPHIC REFERENCES: Bradley, M.O., and Sharkey, N.A.: Mutagenicity and Toxicity of Visible Flourescent Light to Cultured Mammalian Cells. Nature 266, 724-726, 1977. Bradley, M.O.: Regulation of Protein Degradation in Normal and Transformed Human Cells. J. Biol. Chem., in press, 1977.